Diabetes Mellitus Practical Book & Study Guide 2024 v5 (PDF)

Diabetes Mellitus DM is metabolic disorder due to Absolute or Relative insulin deficiency Laboratory tests: - HbA1C > 6.5% - The test reflects the average plasma glucose concentration over a 2-3 month period of time. - It measures the amount of glucose activity associated with red blood cells o...

Diabetes Mellitus DM is metabolic disorder due to Absolute or Relative insulin deficiency Laboratory tests: - HbA1C > 6.5% - The test reflects the average plasma glucose concentration over a 2-3 month period of time. - It measures the amount of glucose activity associated with red blood cells over a 3 month time period (equal to the lifespan of the red blood cell). - Fasting plasma glucose > 126 mg/dL (7.0 mmol/l). (Fasting is defined as no caloric intake for at least 8 h). - Two hours postprandial plasma glucose > 200 mg/dL Treatment of Diabetes Mellitus Physiological insulin replacement therapy 1- Basal insulin - To control fasting glucose and suppress overnight hepatic glucose production - Given as NPH BID (twice daily), glargine OD (once daily), or detemir OD-BID. 2-Prandial insulin (Nutritional insulin” or “Bolus insulin) - To control post-prandial glucose spikes - It is given with each meal. - Given as a rapid-acting insulin analogue. - Regular insulin is considered a pre-prandial insulin because it takes about 30 minutes to start working. - Prandial insulins such as insulin lispro, insulin aspart, and insulin glulisine start working in 5 to 10 minutes. - Physiological insulin replacement therapy 3-Correction insulin “sliding scale insulin” - Given to reduce an elevated blood glucose level to a normal range. - Giving correction insulin is the worst way to manage diabetes. - Rather than maintaining normal blood glucose levels, we're actually waiting until hyperglycemia occurs, and then trying to bring it down to normal. - Regular insulin is used. Common insulin regimens used for treatment of type 1 DM Total daily insulin requirement = 0.5 ˣ total weight in kgs For premixed insulin= 0.5 ˣ total weight in kgs Step 1: calculate total daily insulin requirement; body weight (kg) ̸ 2 (e.g.: for 60 kg pt., total = 30 units) Step 2: then divide this dose into 3 equal parts; (10+10+10) Step 3: give 2 parts in the morning and one part in the evening (morning= 20 U and evening= 10 U) Basal-Bolus insulin regimen: Using Long-acting insulin (glargine/detemir or NPH), once or twice a day with short acting insulin (aspart, glulisine, lispro, Regular) before meals. 1  Example: 60 kg adult with moderate Ketones Total Insulin dose: 30 units Divide Insulin as following: Insulin Glargine (Lantus): 15 units at bedtime Insulin Lispro: 15 units total divided over meals Before breakfast: 5 units, Before lunch: 5 units, Before dinner: 5 units Factors affecting Insulin Requirements: Factors that INCREASE: i) Infection, operation, pregnancy and trauma ii) Treatment with counter-regulating hormones and drugs: - Thiazide diuretics and Diazoxide vasodilator - Sympathomimetics. - Oral contraceptives (and estrogens) - Corticosteroids iii) Specific antagonists e.g., insulinase enzyme and insulin antibodies. Factors that DECREASE: i) Physical exercise (Daily insulin requirements are inversely proportional to degree of physical activity). ii) Decrease in caloric intake. Insulin delivery devices: Insulin syringes Insulin pen Insulin jet Insulin pump Common injection sites Abdomen: most preferred site Other sites: Buttocks, thighs and arms. Site Rotation is essential 2  Patient Education Sample of Patient Education and Counseling A) Teach the patient: 1-Diabetes is a lifelong disease that requires lifestyle changes. 2- Early signs and symptoms of hypoglycemia and hyperglycemia. 3- Hypoglycemia is more dangerous, keep a source of sugar. 4- To wear a medical identification bracelet. B) Regular exercise: Exercise program must be individualized and built up slowly. C) Diet Regulation: Important to all diabetic patients. I- Total Caloric Intake: 1- Depends on Age, Physical activity & Deviation form ideal weight: a- Average weight (30 C/kg). b- Underweight (40 C/kg). c- Overweight (20 C/kg). 2- Weight reduction by caloric restriction in obese type II diabetics → Restore sensitivity to circulating Insulin. 3- Type I diabetics are seldom obese. Adequate diet is essential for growing children. II- Dietary Composition: 1- CHO: 50% of total caloric intake, mainly complex. 2- Proteins: 20% of total caloric intake. 3- Fat: < 30% of total caloric intake (Plant oil is better than Animal fat): a- Unsaturated fat e.g., Olive oil & Palm oil. b- Saturated fat e.g., Butter & Ghee. c- Cholesterol intake < 300 mg/day. 4- Dietary fibers e.g., Bran, green vegetable & fruits → ↓↓Absorption of glucose & cholesterol. III- Timing & Size of Meals: Breakfast should be eaten within 1/2 h after the morning insulin dose. 3 Main meals + 3 Snacks in between and at bed time. VI- Sweeteners: Aspartame, 2 amino-acids (Aspartic acid and Phenylalanine). V- Vitamins: Especially Vit B-1 & B-12. 3  D) Insulin Injection Instructions 1- If meal is OMITTED: Do Not Take Medication. 2- Protect insulin from Heat & Freezing. 3- Store insulin that has not been opened in the Refrigerator. 4- Do Not Shake insulin because of: a- The resulting froth prevents withdrawal of an accurate dose. b- May damage protein molecules. Management of Diabetes Mellitus I- Treatment Type 1 DM: - Life style Modification (Diet regulation + Exercise) + Insulin II- Treatment of Type 2 DM: Step 1 - Life style modifications = Diet + Physical activity Tried for 1 – 3 Months. - If Still Hyperglycemia (HBA1C ≥ 6.5%) → Step 2 - Life style modifications + Monotherapy: Metformin - If Still Hyperglycemia (HBA1C ≥ 6.5%) → Step 3 - Life style modifications + Dual therapy: 1- Metformin + Sulfonylurea (e.g. Glibenclamide or Glipizide) OR 2- Metformin + DPP-4 Inhibitor (Gliptins e.g., Sitagliptin) OR 3- Metformin + SGLT2 inhibitors e.g Dapagliflozin - If Still Hyperglycemia (HBA1C ≥ 6.5%) → Step 4 - Life style modifications + Triple therapy: 1- Metformin + Sulfonylurea + DPP-4 inhibitor (Gliptin) OR 2- Metformin + Sulfonylurea + GLP-1 analogs e.g. Exenatide OR 3- Metformin + Meglitinides (Glinides) + DPP-4 inhibitor OR 4- Metformin + Meglitinides (Glinides) + GLP-1 agonist. - If Still Hyperglycemia (HBA1C ≥ 6.5%) → Step 5 - Life style modifications + Insulin 4  Endocrine Emergencies-Diabetes mellitus emergency cases I- Hypoglycemic coma: - Results in Neuro-glyco-penia: Hunger, headache, irritability, weakness, blurring of vision, confusion, convulsions & coma. - If prolonged → Sweating, pallor, tachycardia & tremors → Permanent brain damage & Death. - Hypoglycemic Coma is the MOST Serious & Common coma in DM - It is due to: 1- Excess insulin 2- Too little meal 3- Excess exercise Management of hypoglycemic coma: If patient is conscious → Oral glucose or sweets If patient in Coma = Unconscious → I.V. Glucose 50 ml 25% → Life-saving. If sterile glucose is not available → Glucagon 1 mg S.C. or I.M II- Hyperglycemic coma: 1-DKA: diabetic ketoacidosis: more in T1DM 2-Euglycemic DKA (E-DKA): more with SGLTi 3-HONK (HyperOsmolar Non Ketotic Hyperglycemia): more in T2DM Diabetic ketoacidosis Treatment: 1- Soluble insulin: 0.1 U/kg/hr IV of Regular Insulin - continue IV insulin until the glucose and acidosis are corrected then switch to SC insulin. 2- Saline [0.9 %NaCL] IV infusion: Rehydration 3- Glucose 5% IV infusion when blood glucose is < 250 mg/dl to avoid hypoglycemia 4- NaHCO3 for severe metabolic acidosis (pH < 7.1; HCO3 < 5). 5- KCl added to IV fluids to avoid hypokalemia during insulin therapy. 6- Antibiotics for infection. Non-Ketotic Hyperosmolar Diabetic Coma - Occurs in Mainly T2DM with bad compliance. - Severe Hyperglycemia→ Polyuria→ Dehydration→ ↑ Osmolarity of Blood→ disturbed conscious level & coma BUT: No ketone bodies formation → no acidosis - Same lines of treatment for DKA But no need to alkalis. - After recovery →Resume Oral anti-diabetic therapy. 8  Thyroid Emergencies Myxedema Coma Definition: severe, long-standing hypothyroidism Treatment: 1-ttt of symptoms: Supportive care 2-ttt of the cause and ppt factor: Abs for infection 3-ttt of myoxedma: a- Loading dose of I.V levothyroxine: usually loading dose of 300–400 mcg initially, followed by 50–100 mcg daily. OR Liothyronine (T3) I.V: 5–20 mcg initially, followed by 2.5–10 mcg every 8 hours, but may be more cardiotoxic and more difficult to monitor. N.B. Intravenous therapy is mandatory because of impaired absorption of drugs in this condition. b- Hydrocortisone: i.v. is also needed, as adrenocortical insufficiency is usually present. Thyroid crisis (storm) - It is a rare but severe and potentially life-threatening complication occurring in untreated hyperthyroid patients; precipitated by surgery, severe infection or illness. - During thyroid storm, an individual's heart rate, blood pressure, and body temperature can increase to dangerously high levels. Management: 1. Methimazole blocks hormone synthesis while propylthiouracil in addition Prevent conversion of T4 to T3 2. K Iodide to inhibit release of thyroid hormones 3. Beta blockers IV without sympathomimetics activity (propranolol): If BB is contraindicated diltiazem can be used 4. Hydrocortisone IV: Protect against shock & Prevent conversion of T4 to T3 5. Supportive therapy is essential to control fever, heart failure, and any underlying disease process that may have precipitated the acute storm. 9  Adrenal Emergencies- Acute Adrenal Insufficiency Clinical Picture of Addisonian crisis: Acute Adrenal Insufficiency- History Investigations: Weakness-Fatigue-Anorexia-Dizziness/ I- Main & Initial Investigations Syncope Blood glucose (both bedside and Nausea / vomiting-Weight loss formal): low in cortisol deficiency Confusion-Seizure Electrolytes: ↑K &↓Na indicates Screen for infective symptoms or injury as a mineralocorticoid deficiency trigger for presentation ABG: Acidosis indicates Examination mineralocorticoid deficiency Hypotension, tachycardia II- Additional investigations: if first Pigmentation in skin creases, nail bed or scars presentation (prior to steroid (may be present in primary adrenal failure) administration if possible): Cortisol Confusion → coma level, ACTH level Acute Adrenal Insufficiency-treatment: 1- Steroid replacement - Give IV bolus/I.M of 50-100 mg/m2 hydrocortisone (Solu-CortefTM) immediately (dose for age shown below). - Follow with hydrocortisone 6 hourly IV - Once stable, 1- Reduce the IV dose, 2- Switch to oral maintenance dose 3-Mineralocorticoid replacement: fludrocortisone (0.05 - 0.1 mg daily). 2- Intravenous fluids: Indication: Shock or moderate to severe dehydration Bolus: 0.9% sodium chloride (normal saline) 10-20 mL/kg during the first hour of treatment. Maintenance: 0.9% sodium chloride and 5% glucose Monitor: RBG (Random Blood Glucose) & Electrolytes (Na+, K+) 3- To Treat hypoglycemia: Bolus: IV of 10% dextrose 2-5 mL/kg and recheck RBG (random blood glucose) after 30 min Maintenance: 10% dextrose in 0.9% sodium chloride to maintain normoglycaemia 4- To Treat Hyperkalemia: monitor by ECG: If Potassium is >7.0 mmol/L + ECG changes (peaked T waves ± wide QRS) → Arrhythmia → Treat with either calcium gluconate or insulin infusion Replacement Therapy in Addison’s disease a- Acute Addisonian Crisis: - Cortisol I.V. → I.V. infusion / 6 hours - Saline + Glucose 5% + Blood transfusion +Vasopressors. b- Chronic Addison’s Disease:→ Orally - Glucocorticoids: hydrocortisone (identical to natural cortisone) ) + Generous salt & sugar diet. - Mineralocorticoids: Fludrocortisone (Mineralocorticoid + some glucocorticoid activity) 10  Calcium Emergencies Hypercalcemia Manifestations: CNS effects: Lethargy Weakness, Confusion Coma Renal effects: Polyuria- Dehydration, Renal stones Gastrointestinal: Constipation, Nausea-Anorexia, Pancreatitis-Gastric ulcer Cardiac effects → syncope from arrhythmias Bone → Bony pains Treatment: Mild hypercalcemia, tends to be asymptomatic. If symptoms are present, they tend to be nonspecific and do not require immediate treatment. Moderate to severe hypercalcemia →immediate attention. 1- The first step is I.V FLUIDS -Intravenous fluid with isotonic saline is the fluid of choice because it helps to facilitate urinary calcium excretion. - Within the first few hours 500 mL then 150 to 200 mL/hour till euvolemia 2- Furosemide: can be considered in certain situations to further increase urinary calcium excretion (especially if renal impairment or cardiac dysfunction is present) 3- Calcitonin (S.C or IM) Dose: 200 units every 8 to 12 hours. M.O.A: Calcitonin reduces bone resorption, Advantages: Rapid onset -within 12 hours Disadvantages: - It is NOT very potent (reduces the serum Ca by no more than 1 to 2 mg/dL) & short- lived. 4- Bisphosphonates M.O.A.: inhibitor of osteoclast-mediated bone resorption Because intravenous or parenteral therapy is required, the two choices are: Dose: pamidronate (30, 60, or 90 mg) or zoledronic acid (4 mg) Advantage: more potent than calcitonin Disadvantages: delayed onset, be cautious or better avoided in renal impairment and follow up kidney function highly recommended 5- Cytokine (RANKL inhibitor) → denosumab - RANK ligand is a powerful bone-resorbing cytokine. It is often stimulated in the context of acute hypercalcemia. M.O.A: The RANK ligand inhibitor, denosumab Dose: (60 or 120 mg given subcutaneously; 120 mg is the approved dose for Hypercalcemia of malignancy) Advantage over the bisphosphonates is that renal dysfunction is not a contraindication. Disadvantages: delayed onset like the bisphosphonates, requires 24 to 48 hours. What are the practitioners doing? - Because both the bisphosphonates and denosumab are not immediately acting a standard of many practitioners faced with this situation is to use combination therapy with calcitonin and either a bisphosphonate or denosumab. - In this way one takes advantage of the rapid but weak effects of calcitonin while waiting for the more delayed but more powerful anticalcemic effects of pamidronate, zoledronic acid, or denosumab to manifest themselves. 11  HypoCalcemia Main causes: Postoperative hypocalcemia, (post-thyroidectomy or post-parathyroidectomy) Assessment Measuring PTH and Ca postoperatively. Treatment Indications: - Total Ca< 7 mg/dL - Ionized calcium < 1.1 mmol/L - Carpopedal spasm - Perioral numbness, - Positive Chvostek’s sign (twitching facial muscles) Chvostek’s sign Trousseau's sign (Carpopedal sapsm) Treatment: Mild: Supplementing with oral calcium (1 to 3 g daily of elemental calcium Moderate: Ca< 7 mg/dL despite calcium supplementation Ca escalated to include up to 6000 mg calcium per day, Vit D-( 0.5 -1 μg of calcitriol twice daily can be added. IV calcium if severe symptoms are present. IV Mg of 1 mg/kg / hour if patients remain symptomatic and hypocalcemic. In severe Refractory hypocalcaemia: Bolus IV injection: 1 to 2 g of calcium in 50 mL of 5% dextrose over 20 min Maintenance IV infusion: 11 g of calcium gluconate in 1000 isotonic saline or D5W. Over 24 Hrs Precaution for Calcium Infusion 1-Slow infusion 2-Clinical Monitoring: pulse and cardiac auscultation to detect early tachycardia 3-ECG: continuous ECG monitoring, as rapid replacement can elicit cardiac arrythmias. 4-Magnesium levels should also be checked Hypomagnesemia (serum magnesium level is below 1.7 mEq/L) and corrected ROLE Of Vitamin D3 Mild: follow up Moderate: calcitriol therapy at 0.25 μg once or twice a day for moderate Severe hypocalcemia: 0.5 μg once or twice a day or if 1-hour postoperative parathormone level is less than 15 pg/mL. Precaution for Vitamin D3: 1- Patients with borderline renal function 2- Elderly. - In these latter two situations, hypercalcemia can occur rather quickly especially when taken with Ca supplement. 12